Preparation of guaiazulene by sulfur



United States Patent i PREPARATION OF GUAEAZULENE BY SULFUR DEHYDROGENATION OF TERPENE-TYPE COM- POUNDS Sanford L. Steelman, Elmhurst, and Frank J. Lindsetl Oak Park, 111., assignors to Armour and Company, Clncago, 111., a corporation of Illinois No Drawing. Application July 23, 1952, Serial No. 300,526

8 Claims. (Cl. 260675.5)

This invention relates to a dehydrogenation process, and the invention is particularly useful in the sulphur dehydrogenation of terpene-type compounds.

An object of the present invention is to provide a process for the dehydrogenation of terpene-type compounds whereby the yield can be substantially increased from 50% to 100%. A further object is to provide a process involving the sulphur dehydrogenation of terpenetype compounds wherein by the introduction of an inert hydrocarbon diluent, a great increase in yield is brought about. Yet another object is to provide a process for the treatment of terpene-type compounds which yield guaiazulene upon dehydrogenation with sulphur, wherein the use of an inert hydrocarbon diluent increases yields of guaiazulene from 50 to 100%, the latter product being useful as an anti-inflammatory agent and for other uses. Other objects and advantages will appear as the specification proceeds.

In one embodiment of our invention, a terpene-type compound is mixed with sulphur and to the mixture is added an inert hydrocarbon diluent, preferably in larger amount than the terpene-type compound, and the mixture is then heated to a dehydrogenation temperature. In an hour or more, the dehydrogenation is found to be complete.

The material may be further processed to recover the dehydrogenated product. As a more specific example, the following may be set out:

35 grams of guaiac wood oil (about 70% guaiol) were mixed with 70 g. of paraflin wax and 15 g. of powdered sulphur. The mixture was heated to 185-190 C. and held for one to one and a half hours. During this interval the dehydrogenation was essentially completed. A vacuum of 10-20 mm. was then applied and the temperature of the mixture was raised to 215-225 C. At this point the guaiazulene distilled and was collected. It was then purified by standard procedures. A yield of 9.8 g. of guaiazulene picrate was obtained.

In the embodiment described above, any terpene-type compound may be employed. The term terpene-type compound as used in this application is intended to refer to the terpenes and analogs thereof having the terpene-type nucleus or ring structure, such as the terpenes, sesquiterpenes, sesquiterpene alcohols, etc. We prefer to employ a terpene-type compound, such as a natural terpene, sesquiterpene, or sesquiterpene alcohol, which yields guaiazulene upon dehydrogenation with sulphur. Among these are guaiol, guaiene, partheniol, aromadendrene, ledol, ledene and a-gurjuene.

While any suitable dehydrogenating agent may be used, we prefer to employ sulphur in a crystalline or amorphous form.

As a diluent, we prefer to use an inert hydrocarbon as, for example, any straight or branched chain hydrocarbon which is inert with the materials of the mixture and at the temperatures usually employed in dehydrogenation procedures. We prefer to use more diluent than terpenetype compound, and we have found that when the diluent 2,734,931 Patented Feb. 14, 1956 is about twice that of the amount of terpene-type compound by weight, a very high yield is obtained. Greater amounts of diluent may be used, but the yield is not greatly increased over that obtained when the diluent is about twice the amount of the terpene-type compound.

It was unexpected that the introduction of an inert hydrocarbon diluent would improve the dehydrogenation process so as to greatly increase the yield, and we were surprised to. find that the introduction of the inert hydrocarbon diluent increased the yields from 50 to 100%.

Specific examples illustrating the process may be set out as follows:

Example I The mixture begins to give ofi H2S after about 15 minutes.

After heating, the oil bath is allowed to cool to about 150 C. and a full vacuum (water aspirator) applied. The temperature of the oil bath is then raised to 215-225 C. and the blue colored azulene distilled over until there is very little evidence of any blue color in the Claisen flask. The blue fraction distills at about 150180 C. at 8-15 mm. This fraction is not pure guaiazulene and must be purified further.

The blue oil from 35 g. of guaiac wood oil is taken up in 250 ml. Skelly F (a solvent manufactured and sold by the Skelly Oil Company, Solvents Division, Kansas City, Missouri, comprising petroleum ether having a boiling range from about 95 to 140 F.) and separated from any water or other insoluble materials present. The Skelly layer is placed in a 500 ml. ground glass stoppered flask and cooled to 510 C. ml. of H3PO4 (previously chilled) is added and the two shaken until the Skelly layer is no longer blue (it usually is a faint green or brown). The Skelly layer is carefully decanted and the H3PO4 layer washed twice with 150-200 ml. of Skelly. After washing the acid layer is poured into 1.5-2 liters of ice water and mixed thoroughly. The phosphoric acid-azulene complex is broken and the azulene separates out as a blue oil. The ice water is extracted with ether (1 gallon in 2 parts) and the other layer dried with Na2SO4. The ether is then removed and the residue taken up in 150 ml. Skelly F. A column of alumina (Harshaw Al-0109-p) 2" x 8" is prepared and the azulene-Skelly solution placed on it. Skelly F is used to develop and elute. The azulene passes through the column very rapidly leaving the green and yellow pigments behind. The eluate is evaporated and the residue weighed (8-9 g.).

The residue is then treated with 1.25 times its weight of picric acid and 10 times its weight (or volume) of alcohol. The mixture is heated to boiling and filtered if necessary. Upon cooling the solution, the guaiazulene picrate crystallizes. The yield is about 10-12 g. of picrate. The mother liquor is concentrated and an additional amount of guaiazulene picrate is obtained from it. The picrate is then recrystallized from 50-75 cc. of alcohol. The yield is about 9.5-10 g. of picrate melting at 123-124 C. (uncorn). The M. P. of pure guaiazulene picrate is 122 C. The yield was approximately 20.1%.

Example II The process was carried out as described in Example I except that no hydrocarbon was added and g. of the guaiac wood oil was used. The yield was 10.8%.

In a similar test, the hydrocarbon diluent was omitted 3 and 70 g. of the guaiac wood oil was used, the yield being A number of other tests were made employing no hydrocarbon diluent and using various percentages of guaiac wood oil, the yield in each case being about 10 or 11%.

Example III 35 g. of guaiac wood oil was mixed with 35 g. of parafiin wax and '15 g. of sulphur and treated as described in Example I. The yield was 15.5% of guaiazulene.

Example IV The process was carried out as described in Example I except that to the 35 g. of guaiac wood oil, 140 g. of paraffin wax was added. The yield was 20.6%..

Example V The process was carried out substantially as described in Example I, except that guaiene was used and the paraffin hydrocarbon was substantially twice the amount of the guaiene. A yield of guaiazulene of approximately was obtained.

Example VI g. of guaiac wood oil, 70 g. of'Dee Tee, a yellow amorphous wax having M. P. 60-63" C. and 15 g. of sulphur, were stirred at ISO-190 C. for 1 /2 hours. The reduced pressure yielded 2.6 grams of crude oil, 3.0 grams of the picrate from which 1.3 grams of guaiazulene was recovered.

Example VII Tests similar to the foregoing were carried on employing an inert solvent of the paraffin hydrocarbon class having its boiling-point above 285 C. The C16 to C24 parafiin hydrocarbons are satisfactory inert solvents for use in the process described.

While in the foregoing specification, we have set forth a specific process inconsiderable detail illustrating an embodiment of the invention, it will be understood that such details of procedure may be varied widely by those skilled in the art without departing from the spirit of our invention.

We claim:

1. In a process for preparing guaiazulene from a terpene-type compound which is convertible to guaiazulene by sulphur dehydrogenation, said terpene-type compound being selected from the group consisting of terpenes, sesquiterpenes, and sesquiterpene alcohols, the steps of mixing said terpene-type compound with sulphur and an inert hydrocarbon diluent, and then heating the mixture to a dehydrogenation temperature to effect de- 4 hydrogenation of said terpene-type compounds and convert it to guaiazulene, said hydrocarbon being the major component of said mixture and having a higher boiling point than the said terpenc-type compound.

2. The process steps of claim 1 in which said terpenetype compound is a sesquiterpene alcohol.

3. The process steps of claim 1 in which said inert hydrocarbon diluent is paraffin wax.

4. -In a process for preparing guaiazulene from guaiolcontaining oil, the steps of mixing the guaiol-containing oil with sulphur and parafiin wax, and then heating the mixture to a dehydrogenation temperature to effect dehydrogenation of the guaiol and convert it to guaiazulene, said parafi'in wax being the major component of said mixture.

5. In a process for the recovery of guaiazulene, the steps of mixing guaiac wood .oil with parafiin wax and sulphur, heating the mixture to about to C. to effect dehydrogenation, and then distilling themixture under. vacuum at a temperature of about 215-225 C. to recover the guaiazulene product.

6. In a process for the sulphur dehydrogenation of guaiac wood oil, the steps of mixing wood oil, powdered sulphur and parafiin wax, the amount of the paratfin wax being about twice that of the wood oil, heating the mix tune to about 185190 C. to bring about dehydrogenation, and distilling the mixture under vacuum at a temperature of about 215-225 C., and recovering the distilled guaiazulene product.

7. In a process for the sulphurdehydrogenation of sesquiterpene alcohols, the steps of mixing parafiin wax with a sesquiterpene alcohol and sulphur, the paraflin wax being in an amount greater than that of the sesquiterpene alcohol and heating the mixture to a dehydrogenation temperature.

8. In a dehydrogenation process of the character set forth, the steps of mixing a sesquiterpene alcohol and sulphur with parafiin wax and heating the mixture to about 185-190" C. to complete the dehydrogenation, more than one part by weight of said paraffin wax being present for each part of said sesquiterpene alcohol.

Pfau et al.: Helv. Chim. Acta, vol. 19, pages 858-879 (19-36).

Haagen-Smitet al.: I. Am. Chem. Soc., vol. 70, pages 2075-2079 (1948). 

1. IN THE PROCESS FOR PREPARING GUAIAZULENE FROM A TERPENE-TYPE COMPOUND WHICH IS CONVERTIBLE TO GUAIAZULENE BY SULPHUR DEHYDROGENATION, SAID TERPENE-TYPE COMPOUND BEING SELECTED FROM THE GROUP CONSISTING OF TERPENES, SESQUITERPENES, AND SESQUITERPENE ALCOHOLS, THE STEPS OF MIXING SAID TERPENE-TYPE COMPOUND WITH SULPHUR AND AN INERT HYDROCARBON DILUENT, AND THEN HEATING THE MIXTURE TO DEHYDROGENATION TEMPERATURE TO EFFECT DEHYDROGENATION OF SAID TERPENE-TYPE COMPOUNDS AND CONVERT TO GUAIAZULENE, SAID HYDROCARBON BEING THE MAJOR COMPONENT OF SAID MIXTURE AND HAVING A HIGHER BOILING POINT THANT THE SAID TERPENE-TYPE COMPOUND. 